title: Does BCG vaccination protect against childhood asthma? Final results from the Manchester Community Asthma Study retrospective cohort study and updated systematic review and meta-analysis.
abstract: BACKGROUND
  The Manchester Community Asthma Study (MANCAS) found a protective effect against the risk of wheeze at age 6 to 11 years for children given neonatal BCG vaccination. Our subsequent systematic review and meta-analysis suggested that BCG vaccination did not protect against allergic sensitization but might have exerted a protective effect against nonatopic asthma.
  
  
  OBJECTIVE
  We sought to assess whether the protective effect of BCG vaccination on wheeze observed in the MANCAS cohort was maintained at age 13 to 17 years and to incorporate the findings from this final MANCAS analysis into an updated systematic review and meta-analysis.
  
  
  METHODS
  BCG vaccination status was determined from health records and respiratory outcomes from questionnaire responses. We updated the systematic review and used fixed-effects and random-effects modeling to undertake meta-analyses.
  
  
  RESULTS
  There were 1608 participants in the final MANCAS analysis. The 12-month prevalence of wheeze was 15.1%. There was no difference in prevalence between those who were and were not BCG vaccinated (15.8% vs 14.3%; relative risk, 1.05; 95% CI, 0.94-1.19). The updated meta-analysis incorporated 4 new studies: this showed that the protective effect of BCG vaccination against the development of asthma identified in our previous meta-analysis was attenuated (odds ratio, 0.95; 95% CI, 0.89-1.00). No protective effect of BCG was seen for sensitization, eczema/atopic dermatitis, rhinoconjunctivitis, or allergy in general.
  
  
  CONCLUSIONS
  Taken together, the final results of the MANCAS cohort and the updated systematic review and meta-analysis provide clearer evidence that any protective effect of BCG vaccination on childhood asthma is likely to be transient.
authors.affiliation: University of Manchester, Manchester Academic Health Science Centre, University Hospital South Manchester NHS Foundation Trust, NIHR South Manchester Respiratory and Allergy Clinical Research Facility, Manchester, United Kingdom. Electronic address: mary.linehan@manchester.ac.uk.
authors.forename: Mary F
authors.initials: MF
authors.lastname: Linehan
authors.affiliation: Allergy and Respiratory Research Group, Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Ulugbek
authors.initials: U
authors.lastname: Nurmatov
authors.affiliation: University of Manchester, Manchester Academic Health Science Centre, University Hospital South Manchester NHS Foundation Trust, NIHR South Manchester Respiratory and Allergy Clinical Research Facility, Manchester, United Kingdom.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Frank
authors.affiliation: University of Manchester, Manchester Academic Health Science Centre, University Hospital South Manchester NHS Foundation Trust, NIHR South Manchester Respiratory and Allergy Clinical Research Facility, Manchester, United Kingdom.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Niven
authors.affiliation: University of Manchester, Manchester Academic Health Science Centre, Clinical Epidemiology and Public Health Unit, Manchester, United Kingdom.
authors.forename: David N
authors.initials: DN
authors.lastname: Baxter
authors.affiliation: Allergy and Respiratory Research Group, Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom; Division of General Internal Medicine and Primary Care, Brigham and Women's Hospital/Harvard Medical School, Boston.
authors.forename: Aziz
authors.initials: A
authors.lastname: Sheikh
mesh_terms: D000293:Adolescent; D000485:Allergens / Q000276:immunology; D001249:Asthma / Q000517:prevention & control*; D001500:BCG Vaccine / Q000276:immunology*; D002648:Child; D015331:Cohort Studies; D006801:Humans; D015995:Prevalence; D012135:Respiratory Sounds; D012189:Retrospective Studies; D014611:Vaccination
chemical_list: D000485:Allergens; D001500:BCG Vaccine
keywords: BCG; Wheeze; allergy; asthma; atopy; children; meta-analysis; systematic review